Present information suggests that host immune responses to specific oral microorganisms play an important role in caries and peridontal disease. It is not clear whether this role is protective or destructive. Animal studies indicating that, in caries, the host salivary IgA response can be protective in nature, have prompted continued efforts to develop a caries vaccine. The purpose of the proposed research is to determine which combination of strain, antigen dose, and route of immunization results in optimal stimulation of the salivary IgA response in mice, and to characterize the cellular events underlying this secretory immune response. A sensitive radioimmunoassay will be used to quantitate specific antibody molecules in six immunoglobulin classes directed against sheep red blood cell surface antigens. Experiments using genetically defined inbred, hybrid, and backcross mice and oral administration of antigen will determine the number of genes involved and the nature of genetic control of secretory immune responsiveness. The effects of route of immunization will be studied by immunizing groups of animal parenterally, orally, intra-gastrically, and by injection of the salivary glands and Peyer's patches. Appropriate dose-response studies will be included. The source of salivary Iga precursor cells will be studied in a cell transfer system, in which sensitized Peyer's patch and mesenteric lymph node cells will be transferred to normal, syngeneic recipients, whose saliva will be tested for Iga antibody. The potential regulatory relationships between the secretory and systemic immune systems will be defined in a passive antibody transfer system. It is hoped that this research will contribute to the development of an effective caries vaccine, and a better understanding of the role of the host immune response in peridontal disease.